Triclosan regulates the Nrf2/HO‐1 pathway through the PI3K/Akt/JNK signaling cascade to induce oxidative damage in neurons

Abstract

Triclosan (TCS), a broad‐spectrum antimicrobial agent, is recognized as an environmental endocrine disruptor. TCS has caused a wide range of environmental, water and soil pollution. TCS is also still detected in food. Due to its high lipophilicity and stability, TCS can enter the human body through biological enrichment and potentially threatenes human health. In recent years, the neurotoxic effects caused by TCS contamination have attracted increasing attention. This study was designed to investigate the mechanism underlying TCS‐induced HT‐22 cells injury and to explore the effect of TCS on the PI3K/Akt, MAPK, and Nrf2/HO‐1 signaling pathways in HT‐22 cells. In this study, we examined the adverse effects of TCS treatment on ROS generation, and MDA, GSH‐Px, and SOD activities. The expression levels of proteins in the Nrf2, PI3K/Akt, MAPK pathways and Caspase‐3, BAX, Bcl‐2 were measured and quantified by Western blotting. The results showed that TCS could significantly reduce the activity of HT‐22 cells, increase the production of intracellular ROS and upregulate the expression of proapoptotic proteins. In addition, TCS promoted an increase in the MDA and SOD levels, and downregulated the GSH‐Px activity, and oxidative damage occurred in neurons. The mechanism underlying this toxicity was related to TCS‐induced PI3K/Akt/JNK‐mediated regulation of the Nrf2/HO‐1 signaling pathway. This result was further confirmed by the specific inhibitors LY294002 and SP600125. In summary, TCS could induce oxidative damage in HT‐22 neurons, and activation of the PI3K/Akt/JNK/ Nrf2 /HO‐1 signaling cascade was the main mechanism underlying the TCS‐induced HT‐22 neuronal toxicity.

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